The dual blocking assay has been used to investigate the relationships between molecules on the cell surfaces of mouse thymocytes and lymphocytes. In this assay the approximation of any two molecules is determined by the ability of antibody to one to block the attachment of antibody to another. In the past year we have been investigating the topographical relationships of mouse alloantigens recognized by hybridoma antibodies. We have found that monoclonal antibodies to Thy-1 will block the subsequent attachment of anti-Ly1, anti Ly2, and anti-H-2D but not anti-H-2K to the fixed or unfixed thymocyte cell surface. In contrast, anti-Ly1, anti-Ly2, anti-H-2D and anti-H-2K will not block the attachment of anti-Thy-1. The pattern is similar to the one obtained with alloantisera and suggests that these relationships may have functional importance. At the very least they imply that caution should be observed in interpreting the results of functional blocking assays where antibody has been used to block specific immune activities.